Iron-mediated ligand-to-metal charge transfer enables 1,2-diazidation of alkenes

Given the widespread significance of vicinal diamine units in organic synthesis, pharmaceuticals and functional materials, as well as in privileged molecular catalysts, an efficient and practical strategy that avoids the use of stoichiometric strong oxidants is highly desirable. We herein report the application of ligand-to-metal charge transfer (LMCT) excitation to 1,2-diazidation reactions from alkenes and TMSN3 via a coordination-LMCT-homolysis process with more abundant and greener iron salt as the catalyst. Such a LMCT-homolysis mode allows the generation of electrophilic azidyl radical intermediate from Fe–N3 complexes poised for subsequent radical addition into carbon–carbon double bond. The generated carbon radical intermediate is further captured by iron-mediated azidyl radical transfer, enabling dual carbon–nitrogen bond formation. This protocol provides a versatile platform to access structurally diverse diazides with high functional group compatibility from readily available alkenes without the need of chemical oxidants.


Supplementary Methods
All reactions were performed in flame-dried glassware using conventional Schlenk techniques under a static pressure of nitrogen unless stated otherwise. Liquids and solutions were transferred with syringes. Solvents were dried and purified following standard procedures. Technical grade solvents for extraction or chromatography (npentane, ethyl acetate, and ethanol) were distilled prior to use. Analytical thin layer chromatography (TLC) was performed on ALUGRAM ® Xtra SIL G/UV254 TLC-Sheets by Macherey-Nagel. Flash column chromatography was performed on silica gel 60 (40-63 µm, 230-400 mesh, ASTM) by Grace using the indicated solvents. 1 H, 13 C, and 19 F NMR spectra were recorded in CDCl3 on Bruker AV400 or AV500 instruments. Chemical shifts are reported to 0.01 ppm for 1 H NMR to 0.01 ppm for 13 C NMR and 19 F NMR spectra. Reference peaks for chloroform in 1 H NMR and 13 C NMR spectra were set at 7.26 ppm and 77.0 ppm, respectively. Data were reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants (Hz), and integration. Gas liquid chromatography (GLC) was performed on an Agilent Technologies 7820A gas chromatograph equipped with a HP-5 capillary column (30 m × 0.32 mm, 0.25 µm film thickness) by Agilent Technologies/CS-Chromatographie Service using the following program: N2 carrier gas, injection temperature 250 °C, detector temperature 300 °C, flow rate: 1.7 mL/min; temperature program: start temperature 40 °C, heating rate 10 °C/min, end temperature 280 °C for 10 min.   atmosphere. The reaction tube was then sealed and was placed at a distance (app. 5 cm) from a 40 W blue kessil lamp ( Figure S2). The reaction mixture was stirred for 36 h at room temperature. After the reaction, the resulting solution was filtered through a cotton plug and washed with EtOAc. The filtrate was removed under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/npentane) to afford the desired diazide 2i (0.87 g, 75%).

Reaction condition optimization
A 100 mL Schlenk tube equipped with a magnetic stir bar was charged with Fe(NO3)3· 9H2O (6.6 mmol, 2.45 g). Then, the tube was evacuated and backfilled with Ar (three times). 8-bromooct-1-ene (1,14 g, 6.0 mmol, 1.0 equiv.) and TMSN3 (25 mmol, 2.88 g) in CH3CN (60 mL) were added by syringe under Ar atmosphere. The reaction tube was then sealed and was placed at a distance (app. 5 cm) from a 40 W blue kessil lamp ( Figure S2). The reaction mixture was stirred for 36 h at room temperature. After the reaction, the resulting solution was filtered through a cotton plug and washed with EtOAc. The filtrate was removed under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/n-pentane) to afford the desired diazide 2q (1.29 g, 75%).
A 10 mL Schlenk tube equipped with a magnetic stir bar was charged with Fe(NO3)3· 9H2O (0.12 mmol, 50 mg). Then, the tube was evacuated and backfilled with Ar (three times). Alkene (23.8 mg, 0.10 mmol, 1.0 equiv.) and TMSN3 (0.44 mmol) in CH3CN (2 mL) were added by syringe under Ar atmosphere. The reaction tube was then sealed and was placed at a distance (app. 5 cm) from a 40 W blue kessil lamp ( Figure S1). The reaction mixture was stirred for 24 h at room temperature.

The analysis for the reaction mixture by GC-MS
A 10 mL Schlenk tube equipped with a magnetic stir bar was charged with Fe(NO3)3· 9H2O (0.24 mmol, 100 mg). Then, the tube was evacuated and backfilled with Ar (three times). Alkene 1a (29.2 mg, 0.20 mmol, 1.0 equiv.) and TMSN3 (1.0 mmol) in CH3CN (2 mL) were added by syringe under Ar atmosphere. The reaction tube was then sealed and was placed at a distance (app. 5 cm) from a 40 W blue kessil lamp ( Figure S1). The reaction mixture was stirred for 24 h at room temperature. The reaction mixture was analyzed by GC-MS.
Supplementary Figure 3. Spectra of the reaction mixture by GC-MS analysis.
Then, the tube was evacuated and backfilled with Ar (three times). Alkene 1a (29.2 mg, 0.20 mmol, 1.0 equiv.) and TMSN3 (1.0 mmol) in CH3CN (2 mL) were added by syringe under Ar atmosphere. The reaction tube was then sealed and was placed at a distance (app. 5 cm) from a 40 W blue kessil lamp ( Figure S1). The reaction mixture was stirred for 24 h at room temperature. The corresponding diazide product 2a was not detected according to both TLC and GC-Mass analysis. The TEMPO-adduct 3 was detected by ESI-HRMS.

Exclusion of radical-polar crossover pathway
A 10 mL Schlenk tube equipped with a magnetic stir bar was charged with Fe(NO3)3· 9H2O (0.24 mmol, 100 mg). Then, the tube was evacuated and backfilled with Ar (three times). hex-5-en-1-ol (20.0 mg, 0.20 mmol, 1.0 equiv.) and TMSN3 (1.0 mmol) in CH3CN (2 mL) were added by syringe under Ar atmosphere. The reaction tube was then sealed and was placed at a distance (app. 5 cm) from a 40 W blue kessil lamp ( Figure S1). The reaction mixture was stirred for 24 h at room temperature. After the reaction, the resulting solution was filtered through a cotton plug and washed with EtOAc. The filtrate was removed under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate/n-pentane) to afford the product 5,6-diazidohexan-1-ol (23.9 mg, 65% yield) as an oil. And no cyclic product was observed by MS analysis.
The intermolecular trapping experiments were performed with a large excess of nucleophiles such as H2O and EtOH added into reaction system, however, the compounds trapped by nucleophiles could not be detected. A radical-polar crossover mechanism should be excluded.